key: cord-318808-1cfwj5uq
authors: Li, Ying; Wang, Haizhou; Wang, Fan; Du, Hui; Liu, Xueru; Chen, Peng; Wang, Yanli; Lu, Xiaoxia
title: Comparison of Hospitalized Patients with pneumonia caused by COVID-19 and influenza A in children under 5 years
date: 2020-06-12
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.06.026
sha: 
doc_id: 318808
cord_uid: 1cfwj5uq

Abstract Background Since the outbreak of Coronavirus Disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to differentiate COVID-19 from other respiratory infectious diseases, such as influenza viruses. Methods This was a retrospective study. Two group of COVID-19 patients (n=57) and influenza A patients (n=59) were enrolled. We analyzed and compared their clinical manifestations, imaging characteristics and treatments. Results The proportions of cough (70.2%), fever (54.4%) and gastrointestinal symptoms (14.1%) in COVID-19 patients were lower than those of influenza A patients (98.3%, P<0.001; 84.7%, P<0.001; and 35.6%, P=0.007; respectively). In addition, COVID-19 patients showed significantly lower levels of leukocytes (7.87 vs. 9.89×109/L, P=0.027), neutrophils (2.43 vs. 5.16×109/L, P<0.001), C-reactive protein (CRP; 3.7 vs. 15.1mg/L, P=0.001) and procalcitonin (PCT; 0.09 vs. 0.68mm/h, P<0.001), while lymphocyte levels (4.58 vs. 3.56×109/L; P=0.006) were significantly higher compared with influenza A patients. In terms of CT imaging, ground-glass opacification in chest CT was more common in COVID-19 patients than in influenza A patients (42.1% vs. 15%, P=0.032). In contrast, consolidation was more common in influenza A patients (25%) than that in COVID-19 patients (5.2%, P=0.025). Conclusion The clinical manifestations and laboratory tests of COVID-19 children are milder than those of influenza A children under 5 years. Additionally, imaging results more commonly presented as ground-glass opacities in COVID-19 patients.

The clinical manifestations of COVID-19 children are milder than those of influenza A children under 5 years.

The laboratory tests of COVID-19 children are milder than those of influenza A children under 5 years.

Imaging results more commonly presented as ground-glass opacities in COVID-19

patients.

Since December 2019, a novel coronavirus has broken out in Wuhan, and spread rapidly worldwide. On February 11, 2020, the World Health Organization (WHO) officially named this novel coronavirus pneumonia as Coronavirus Disease 2019 , whereas the International Committee on Taxonomy of Viruses has named it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On 11 March, WHO declared the COVID-19

should be characterized as a pandemic. As the highly contagious of SARS-CoV-2, the entire population were generally susceptible, including young children. Data from China showed young children were vulnerable to SARS-CoV-2 infection (Dong et al., 2020) . In addition, WHO estimated that more than more than 2 million children under 5 years of age die from pneumonia, accounting for almost one in five under-5 deaths worldwide in 2004 (Wardlaw et al., 2006) . Pneumonia was the leading infectious cause of death in children younger than 5 years (Wardlaw et al., 2006) . Therefore, close attention should be paid to children with pneumonia less than 5 years old during the COVID-19 pandemic.

Influenza viruses have precipitated pandemics several times over the past 100 years, specifically in 1918, 1957, 1968 and 2009 . Influenza A was a common cause of pneumonia in young children (Jain et al., 2015) . Recently, Kong et al retrospectively investigated the presence of SARS-CoV-2 among local patients with influenza like illness (ILI) from 6

October 2019 to 21 January 2020 and found SARS-CoV-2 RNA was detected in nine ILI patient specimens (Kong et al., 2020) . In addition, ILI data for the 2019-2020 winter was significantly higher in comparison to previous years about children, suggested it was necessary to distinguish the difference between influenza A and COVID-19 young children with pneumonia. Therefore, the aim of this study was to compare the different clinical Page 5 of 15 J o u r n a l P r e -p r o o f 5 presentations between patients with infected with COVID-19 pneumonia versus influenza A pneumonia, to provide some recommendations for their differential diagnosis.

Subjects of the study were consecutive children with either confirmed COVID-19 pneumonia (admitted between 28 January and 11 March 2020) or influenza A pneumonia (admitted between 14 December 2019 and 30 February 2020) in Wuhan Children's hospital.

The study was approved by the Research Ethics Board of WuHan Children's Hospital (No. 2020003) . Consent of the patients' legal guardians was obtained.

Children were included in the study if they had evidence consistent with pneumonia as assessed by means of chest radiography or CT within 72 hours before or after admission. The virus nucleic acid detection kit was confirmed COVID-19 patients through detecting the RNA of SARS-CoV-2 in throat swab samples using based on the manufacturer's protocol (Shanghai BioGerm Medical Biotechnology Co.,Ltd). Influenza A was detected by direct immunofluorescence assay. The diagnostic criteria for severe pneumonia caused by SARS-CoV-2 and influenza A conform to guideline (2020, Harper et al., 2009 ).

A COVID-19 or influenza A case report form was designed to document primary data regarding demographic, clinical and laboratory characteristics from electronic medical records. The following information was extracted from each patient: gender, age, medical history, chief complaints, laboratory findings and computed tomography (CT) imaging on admission.

Categorical data were described as percentages, and continuous data as median with standard deviation (SD). Nonparametric comparative test for continuous data and χ 2 test for categorical data were used to compare variables between groups. The statistical analyses were performed using SPSS Statistics version 25.0 software. P<0.05 was considered statistically significant.

A total of 57 COVID-19 patients and 59 influenza A patients were included (Table 1) . No significant differences were found in the median age between COVID-19 patients and influenza A patients (18.7 months vs. 21.8 months, P = 0.121). The proportion of male was also not significantly different between the two groups (61.4% vs. 66.1%, P = 0.599). The most common symptoms and signs were cough (84.5%), fever (69.8%) and gastrointestinal symptoms (25%), whereas dyspnea (6.0%) and convulsions (3.4%) were less common. 

For blood inflammatory indictors, lower levels of C-reactive protein (CRP), procalcitonin (PCT) were observed in COVID-19 patients than influenza A patients ( Table 2 ).

In terms of CT imaging, ground-glass opacification in chest CT was more common in COVID-19 patients than in influenza A patients (42.1% vs. 15%, P = 0.032). In contrast, consolidation was more common in influenza A patients (25%) than that in COVID-19 patients (5.2%, P = 0.025) ( Fig. 1 and Table 3 ). As we found before, cough and fever were the common symptoms in COVID-19 (Lu et al., 2020) , which is similar with influenza A. Our present study revealed that COVID-19 manifested as mild, severe pneumonia were less than influenza A patients. Some COVID-19

patients only presented as fever or cough. Meanwhile, influenza A patients were more likely to be fever with higher temperature. Gastrointestinal symptoms were supposed to be common in patients with COVID-19 (Cheung et al., 2020) , however, were less when compared with influenza A. Convulsions could be found in both patients, but the reason was different, as only one in COVID-19 was secondary to pneumonia and three in influenza A were confirmed as febrile convulsion.

Lymphopenia and raise in D-dimer were the common laboratory abnormality in COVID-19 adult (Huang et al., 2020 and were proved as the caution of severity in COVID-19 (Ruan et al., 2020 , Zheng et al., 2020 . In our study, lymphocyte count and D-dimer were lower in influenza A patients than in COVID-19, which could further prove that COVID-19 is milder than influenza A. Similarly, CRP (C-reactive protein) and PCT (procalcitonin), which was the severity index of pneumonia, were lower in COVID-19 than influenza A.

In our study, we found that ground-glass opacity was more common in COVID-19 patients than in influenza A patients, whereas consolidation was more frequent in influenza A patients, which was consistent with previous studies. The radiological findings of children with COVID-19 pneumonia from our team and other study showed that ground-glass opacities were the most common pattern of abnormalities in chest CT (Chang et al., 2020) .

Additionally, studies on influenza A-associated pneumonia showed that consolidation was common on CT (Guo et al., 2012) . Therefore, these differential pathological changes may contribute to distinguish imaging characteristics during clinical assessments.

There were some limitations of our present study. First, this was a retrospective study that included data from a single-center cohort. We hope for prospective cohort and multi-center study. Second, influenza A was diagnosis by direct immunofluorescence assay and failed to be typed.

In conclusion, COVID-19 patients were mild not only in clinical symptoms but also in laboratory examinations which including lymphocyte, CRP, PCT, D-dimer in the children under 5 years. Additionally, imaging results more commonly presented as ground-glass opacity in COVID-19 patients.

The authors declare that they have no conflict of interest.

This study was approved by the Research Ethics Board of WuHan Children's Hospital (No.

WHCH 2020003).

[ 

Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the

Hong Kong Cohort and Systematic Review and Meta-analysis

Epidemiology of COVID-19 Among Children in China

Radiological findings in 210 paediatric patients with viral pneumonia: a retrospective case study

Seasonal influenza in adults and children--diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Community-Acquired Pneumonia Requiring Hospitalization among U

SARS-CoV-2 detection in patients with influenza-like illness

SARS-CoV-2 Infection in Children

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan

Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Pneumonia: the leading killer of children

MB isoenzyme of creatine kinase; BUN, blood urea nitrogen


